Botox is administered by injection and dosing depends on the condition that it is used for. Administration of botulinum toxin with other agents (for example, aminoglycosides, curare) that affect neuromuscular function may increase the effect of botulinum toxin. There are no adequate studies of Botox in pregnant women and it has not been evaluated in nursing mothers.

Our Botox Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; feeling like you might pass out; swelling of your face, lips, tongue, or throat.

The botulinum toxin contained in Botox can spread to other body areas beyond where it was injected. This has caused serious life-threatening side effects in some people receiving botulism toxin injections, even for cosmetic purposes.

Call your doctor at once if you have any of these serious side effects, some of which can occur up to several weeks after an injection:

trouble breathing, talking, or swallowing;

hoarse voice, drooping eyelids;

unusual or severe muscle weakness (especially in a body area that was not injected with the medication);

loss of bladder control;

problems with vision;

crusting or drainage from your eyes;

severe skin rash or itching;

fast, slow, or uneven heartbeats; or

chest pain or heavy feeling, pain spreading to the arm or shoulder, general ill feeling.

Less serious side effects may include:

muscle weakness near where the medicine was injected;

bruising, bleeding, pain, redness, or swelling where the injection was given;

headache, muscle stiffness, neck or back pain;

fever, cough, sore throat, runny nose, flu symptoms,

dizziness, drowsiness, tired feeling;

nausea, diarrhea, stomach pain, loss of appetite;

dry mouth, dry eyes, ringing in your ears;

increased sweating in areas other than the underarms;

itchy or watery eyes, increased sensitivity to light; or

eyelid swelling or bruising.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in cl inical practice.

BOTOX and BOTOX Cosmetic contain the same active ingredient in the same formulation, but with different labeled Indications and Usage. Therefore, adverse reactions observed with the use of BOTOX Cosmetic also have the potential to be observed with the use of BOTOX.

In general, adverse reactions occur within the first week follo wing injection of BOTOX and while generally transient, may have a duration of several months or longer. Localized pain, infection, inflammation, tenderness, swelling, erythema, and/or bleeding/bruising may be associated with the injection. Needle-related pain and/or anxiety may result in vasovagal responses (including e.g., syncope, hypotension), which may require appropriate medical therapy.

Local weakness of the injected muscle(s) represents the expected pharmacological action of botulinum toxin. However , weakness of nearby muscles may also occur due to spread of toxin [see WARNINGS AND PRECAUTIONS] .

Overactive Bladder

Table 11 presents the most frequently reported adverse reactions in double-blind, placebo-controlled clinical trials for overactive bladder occurring within 12 weeks of the first BOTOX treatment.

Table 11: Adverse Reactions Reported by ≥2% of BOTOX treated Patients and More Often than in Placebo-treated Patients Within the First 12 Weeks after Intradetrusor Injection, in Double-blind, Placebo-controlled Clinical Trials in Patients with OAB

Table 12: Proportion of Patients Experiencing Urinary Tract Infection following an Injection in Double-blind, Placebo-controlled Clinical Trials in OAB according to history of Diabetes Mellitus

Patients with Diabetes

Patients without Diabetes

BOTOX 100 Units (N=81)

Placebo (N=69)

BOTOX 100 Units (N=526)

Placebo (N=516)

Urinary tract infection (UTI)

25 (31%)

8 (12%)

135 (26%)

51 (10%)

The incidence of UTI increased in patients who experienced a maximum post-void residual (PVR) urine volume ≥200 mL following BOTOX injection compared to those with a maximum PVR <200 mL following BOTOX injection, 44% versus 23%, respectively. No change was observed in the overall safety profile with repeat dosing during an open-label, uncontrolled extension trial.

Detrusor Overactivity Associated With A Neurologic Condition

Table 13 presents the most frequently reported adverse reactions in the two Phase 3 double-blind, placebo-controlled studies (NDO-1 and NDO-2) within 12 weeks of injection for patients with detrusor overactivity associated with a neurologic condition treated with BOTOX 200 Units.

Table 13: Adverse Reactions Reported by ≥2% of BOTOX treated Patients and More Frequent than in Placebo-treated Patients Within the First 12 Weeks after Intradetrusor Injection in Double-blind, Placebo-controlled Clinical Trials (NDO-1 and NDO-2)

In the Multiple Sclerosis (MS) patients enrolled in the double-blind, placebo-controlled trials, the MS exacerbation annualized rate (i.e., number of MS exacerbation events per patient-year) was 0.23 for BOTOX and 0.20 for placebo.

No change was observed in the overall safety profile with repeat dosing.

Table 14 presents the most frequently reported adverse reactions in a placebo-controlled, double-blind post-approval 52 week study with BOTOX 100 Units (Study NDO-3) conducted in MS patients with urinary incontinence due to detrusor overactivity associated with a neurologic condition. These patients were not adequately managed with at least one anticholinergic agent and not catheterized at baseline. The table below presents the most frequently reported adverse reactions within 12 weeks of injection.

Table 14: Adverse Reactions Reported by >2% of BOTOX treated Patients and More Frequent than in Placebo-treated Patients Within the First 12 Weeks after Intradetrusor Injection (NDO-3)

No difference in the MS exacerbation annualized rate (i.e., number of MS exacerbating events per patient-year) was observed (BOTOX =0, placebo =0.07).

Chronic Migraine

In double-blind, placebo-controlled chronic migraine efficacy trials (Study 1 and Study 2), the discontinuation rate was 12% in the BOTOX treated group and 10% in the placebo-treated group. Discontinuations due to an adverse event were 4% in the BOTOX group and 1% in the placebo group. The most frequent adverse events leading to discontinuation in the BOTOX group were neck pain, headache, worsening migraine, muscular weakness and eyelid ptosis.

The most frequently reported adverse reactions following injection of BOTOX for chronic migraine appear in Table 15.

Table 15: Adverse Reactions Reported by >2% of BOTOX treated Patients and More Frequent than in Placebo-treated Patients in Two Chronic Migraine Double-blind, Placebo-controlled Clinical Trials

Adverse Reactions by System Organ Class

BOTOX 155 Units-195 Units (N=687)

Placebo (N=692)

Nervous system disorders

Headache

32 (5%)

22 (3%)

Migraine

26 (4%)

18 (3%)

Facial paresis

15 (2%)

0 (0%)

Eye disorders

Eyelid ptosis

25 (4%)

2 (<1%)

Infections and Infestations

Bronchitis

17 (3%)

11 (2%)

Musculoskeletal and connective tissue disorders

Neck pain

60 (9%)

19 (3%)

Musculoskeletal stiffness

25 (4%)

6 (1%)

Muscular weakness

24 (4%)

2 (<1%)

Myalgia

21 (3%)

6 (1%)

Musculoskeletal pain

18 (3%)

10 (1%)

Muscle spasms

13 (2%)

6 (1%)

General disorders and administration site conditions

Injection site pain

23 (3%)

14 (2%)

Vascular Disorders

Hypertension

11 (2%)

7 (1%)

Other adverse reactions that occurred more frequently in the BOTOX group compared to the placebo group at a frequency less th an 1% and potentially BOTOX related include: vertigo, dry eye, eyelid edema, dysphagia, eye infection, and jaw pain. Severe worsening of migraine requiring hospitalization occurred in approximately 1% of BOTOX treated patients in Study 1 and Study 2, usually within the first week after treatment, compared to 0.3% of placebo-treated patients.

Upper Limb Spasticity

The most frequently reported adverse reactions following injection of BOTOX for adult upper limb spasticity appear in Table 16.

Twenty two adult patients, enrolled in double-blind placebo controlled studies, received 400 Units or higher of BOTOX for treatment
of upper limb spasticity. In addition, 44 adults received 400 Units of BOTOX or higher for four consecutive treatments over
approximately one year for treatment of upper limb spasticity. The type and frequency of ad verse reactions observed in patients
treated with 400 Units of BOTOX were similar to those reported in patients treated for upper limb spasticity with 360 Units of
BOTOX.

Lower Limb Spasticity

The most frequently reported adverse reactions following injection of BOTOX for adult lower limb spasticity appear in Table 17. Two
hundred thirty one patients enrolled in a double-blind placebo controlled study (Study 6) received 300 Units to 400 Units of BOTOX,
and were compared with 233 patients who received placebo. Patients were followed for an average of 91 days after injection.

Other events reported in 2-10% of patients in any one study in decreasing order of incidence include: increased cough, flu syndrome, back pain, rhinitis, dizziness, hypertonia, soreness at injection site, asthenia, oral dryness, speech disorder, fever, nausea, and drowsiness. Stiffness, numbness, diplopia, ptosis, and dyspnea have been reported.

Dysphagia and symptomatic general weakness may be attributable to an extension of the phar macology of BOTOX resulting from the spread of the toxin outside the injected muscles [see WARNINGS AND PRECAUTIONS].

The most common severe adverse reaction associated with the use of BOTOX injection in patients with cervical dystonia is dysp hagia with about 20% of these cases also reporting dyspnea [see WARNINGS AND PRECAUTIONS]. Most dysphagia is reported as mild or moderate in severity. However, it may be associated with more severe signs and symptoms [see WARNINGS AND PRECAUTIONS].

Additionally, reports in the literature include a case of a female patient who developed brachial plexopathy two days after i njection of 120 Units of BOTOX for the treatment of cervical dystonia, and reports of dysphonia in patients who have been treated for cervical dystonia.

Primary Axillary Hyperhidrosis

The most frequently reported adverse reactions (3-10% of adult patients) following injection of BOTOX in double-blind studies included injection site pain and hemorrhage, non-axillary sweating, infection, pharyngitis, flu syndrome, headache, fever, neck or back pain, pruritus, and anxiety.

Blepharospasm

In a study of blepharospasm patients who received an average dose per eye of 33 Units (injected at 3 to 5 sites) of the currently manufactured BOTOX, the most frequently reported adverse reactions were ptosis (21%), superficial punctate keratitis (6%), a nd eye dryness (6%).

Other events reported in prior clinical studies in decreasing order of incidence include: irritation, tearing, lagophthalmos, photophobia, ectropion, keratitis, diplopia, entropion, diffuse skin rash, and local swelling of the eyelid skin lasting for several da ys following eyelid injection.

In two cases of VII nerve disorder, reduced blinking from BOTOX injection of the orbicularis muscle led to serious corneal ex posure, persistent epithelial defect, corneal ulceration and a case of corneal perforation. Focal facial paralysis, syncope, and exacerbation of myasthenia gravis have also been reported after treatment of blepharospasm.

Strabismus

Extraocular muscles adjacent to the injection site can be affected, causing vertical deviation, especially with higher do ses of BOTOX. The incidence rates of these adverse effects in 2058 adults who received a total of 3650 injections for horizontal strabismus was 17%. The incidence of ptosis has been reported to be dependent on the location of the injected muscles, 1% after inferior rectus injections, 16% after horizontal rectus injections and 38% after superior rectus injections.

In a series of 5587 injections, retrobulbar hemorrhage occurred in 0.3% of cases.

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibo dy) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to onabotulinumtoxinA in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

In a long term, open-label study evaluating 326 cervical dystonia patients treated for an average of 9 treatment sessions with the current formulation of BOTOX, 4 (1.2%) patients had positive antibody tests. All 4 of these patients responded to BOTOX therapy at the time of the positive antibody test. However, 3 of these patients developed clinical resistance after subsequent treatment , while the fourth patient continued to respond to BOTOX therapy for the remainder of the study.

One patient among the 445 hyperhidrosis patients (0.2%), two patients among the 380 adult upper limb spasticity patients (0.5 %) and no patients among 406 migraine patients with analyzed specimens developed the presence of neutralizing antibodies.

In overactive bladder patients with analyzed specimens from the two phase 3 studies and the open-label extension study, neutralizing antibodies developed in 0 of 954 patients (0.0%) while receiving BOTOX 100 Unit doses and 3 of 260 patients (1.2%) after subsequently receiving at least one 150 Unit dose. Response to subsequent BOTOX treatment was not different following seroconversion in these three patients.

In detrusor overactivity associated with neurologic condition patients with analyzed specimens in the drug development program (including the open-label extension study), neutralizing antibodies developed in 3 of 300 patients (1.0%) after receiving only BOTOX 200 Unit doses and 5 of 258 patients (1.9%) after receiving at least one 300 Unit dose. Following development of neutralizing antibodies in these 8 patients, 4 continued to experience clinical benefit, 2 did not experience clinical benefit, and the effect on the response to BOTOX in the remaining 2 patients is not known.

The data reflect the patients whose test results were considered positive for neutralizing activity to BOTOX in a mouse prote ction assay or negative based on a screening ELISA assay or mouse protection assay.

Formation of neutralizing antibodies to botulinum toxin type A may reduce the effectiveness of BOTOX treatment by inactivating the biological activity of the toxin. The critical factors for neutralizing antibody formation have not been well characterized. The results from some studies suggest that BOTOX injections at more frequent intervals or at higher doses may lead to greater incidence of antibody formation. The potential for antibody formation may be minimized by injecting with the lowest effective dose given at the longest feasible intervals between injections.

Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of BOTOX. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions include: abdominal pain; alopecia, including madarosis; anorexia; brachial plexopathy; denervation/muscle atrophy; diarrhea; hyperhidrosis; hypoacusis; hypoaesthesia; malaise; paresthesia; peripheral neuropathy; radiculopathy; erythema multiforme, dermatitis psoriasiform, and psoriasiform eruption; strabismus; tinnitus; and visual disturbances.

There have been spontaneous reports of death, sometimes associated with dysphagia, pneumonia, and/or other significant debility or anaphylaxis, after treatment with botulinum toxin [see WARNINGS AND PRECAUTIONS].

New onset or recurrent seizures have also been reported, typically in patients who are predisposed to experiencing these events. The exact relationship of these events to the botulinum toxin injection has not been established.